hlab27 il23r和erap1多态性与中国强直性脊柱炎患者的相关性研究-correlation between hlab 27 il23r and era p1 polymorphism and ankylosing spondylitis in china.docx

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hlab27 il23r和erap1多态性与中国强直性脊柱炎患者的相关性研究-correlation between hlab 27 il23r and era p1 polymorphism and ankylosing spondylitis in china.docx

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hlab27 il23r和erap1多态性与中国强直性脊柱炎患者的相关性研究-correlation between hlab 27 il23r and era p1 polymorphism and ankylosing spondylitis in china

INTRODUCTIONDespitetheextensiveamountofresearchthathasbeenconductedoverthepastfewdecades,theexactcauseofAnkylosingSpondylitis(AS)remainsunknown.Investigatorsarepuzzledbytheinsidiousonsetthatleadstodiagnosisonlyafterseveralyears.Thepathogenesisappearstoberelatedtoacomplexinteractionofimmunological,genetic,andenvironmentalfactorswhicharenotyetclearlyunderstood.Scientist,however,hasidentifiedcertainriskfactorsthatmayincreaseaperson’schancesofdevelopingAnkylosingSpondylitis[6][7].EvidenceforapossiblegeneticpredispositiontoASissupportedbythefindingthataspecifcHumanLeucocyteAntigen(HLA)tissuetypeknownasHLA-B27occurs90-95%ofindividualwithAS[4].Incontrast,theHLA-B27geneticmarkerisonlyfoundinabout6%oftheoverallgeneralpopulationsuggestingthatindividualswiththeHLA-B27tissuetypemaybemoregeneticallypredisposedtodevelopingASthanpeoplewhodonotpossessestheHLA-B27geneticmarker.HLA-B27isvirtuallyaprerequisiteforthedevelopmentofASbutonitsownitisinsufficienttocausethedisease.[2]TheoverallprevalenceofASinChinesepopulationis0.2-0.54%amongHanEthnicChinese.[9]HLA-B27isfoundin95%inChinesepatientsascomparedto-5%inhealthy[10]AlthoughHLA-B27isrecognizedtobethemajorgeneassociatedwithAS,aroleforgenesoutsidetheHLAregion(non-MHC)isincreasinglybeingrecognized,amongwhichinterlukin23RandERAP1arerecentlybeensuggestedtobeassociatedwithASbystudiedperformedonagene-targetedassociationstudyof14500ncSNPin1000AScasesand1500controlsbytheWellcomeTrustCaseControlConsortiumandtheAustralo-Anglo-AmericanSpondylitisConsortium(WTCCC-TASC[8][3]in2007.OthergeneshaveshowntobeassociatedwithASinChinesepopulation,includingHLA-B60[11]andIL1A/B(12)(13).RecentstudyhaveshowntheassociationofIL23RwithSpAincludingIBD,psoriaisandASincaucassianpopulation.(17)(18)butithasbeennotdetectedinKoreanandChinesepopulation(16)(14).ButanotherstudycarriedbyWangetalshowstherelationshipbetweenthepolymorphisminIL23RinChinesepopulation(15).AnothergeneticmarkerERAP1whichhasbeenrecentlybeenshowntoassociatedwithASinBritish,NorthAmerican,Portuguese,C